Process for the preparation of trans-(R,R)-actinol

Abstract

A process for the manufacture of trans-(R,R)-actinol by diasteroselective transfer hydrogenation of levodione comprises hydrogenating (R)-levodione in the presence of a hydrogen donor, which simultaneously can be used as the solvent, and an amino-amide-ruthenium complex, especially of the formula RuH(L{-H})(Y), wherein Y signifies a neutral ligand and L signifies an optionally optically active monosulphonylated diamine ligand, as defined in more detail in the description. Moreover, the invention is concerned with some of the amino-amide-ruthenium complexes and with the corresponding precursors to these complexes, which have halogen in place of H. The product of the process in accordance with the invention, trans-(R,R)-actinol, is known as an important building block for the synthesis of carotenoids, e.g. zeaxanthin. By the process trans-(R,R)-actinol is made available in particularly high enantiomeric and diasteromeric purity.

What is claimed is:  
     
       1. A process for the manufactue of trans-(R,R)-actinol (1)                    
       which process comprises hydrogenating (R)-levodione (2)                    
       in the presence of a hydrogen donor and a solvent or in the presence of a hydrogen donor which is simultaneously used as the solvent, and an amino-amide-ruthenium complex. 
     
     
       2. A process of claim  1 , wherein the amino-amide-ruthenium complex has the formula 
       
         
           RuH(L{—H})(Y)  I  
         
       
       wherein 
       Y signifies a neutral ligand, and  
       L signifies a group of formula                    
       wherein 
       R 1  signifies alkyl which may be substituted with one or more fluorine atoms, alkenyl, alkynyl, cycloalkyl, aryl which may be substituted, heteroaryl, or camphor-10-yl,  
       R 2  and R 3  each independently signify hydrogen, alkyl, cycloalkyl, or aryl which may be substituted, or R 2  and R 3  together with —CH—(CH 2 ) n —CH— form a carbocycle with 4 to 8 carbon atoms,  
       R 4  signifies hydrogen or alkyl, and  
       n signifies 0,1,2 or 3.  
     
     
       3. A process of claim  2 , wherein R 2  and R 3  each independently signify hydrogen, alkyl, cycloalkyl or unsubstituted or substituted aryl, or R 2  and R 3  together with —CH—(CH 2 ) n —CH— form a carbocycle with 4 to 6 carbon atoms, and n signifies 0 or 1. 
     
     
       4. A process of claim  2  wherein L signifies a group of formula II in which R 2  and R 3  are both either hydrogen or phenyl, or together with —CH—(CH 2 ) n —CH— form a carbocycle with 4 to 8 carbon atoms, and R 4  signifies hydrogen. 
     
     
       5. A process of claim  4  wherein n signifies 0. 
     
     
       6. A process of claim  2  wherein R 2  and R 3  each independently signify alkyl, cycloalkyl or unsubstituted or substituted aryl, or R 2  and R 3  together with —CH—(CH 2 ) n —CH— form a carbocycle with 4 to 8 carbon atoms. 
     
     
       7. A process of claim wherein R 1  is aryl or heteroaryl and R 2  and R 3  are independently aryl, of which aryl may be unsubstituted or may be substituted with phenyl, halogen, alkyl, or alkoxy. 
     
     
       8. A process of claim  7  wherein R 1  is a five- or six-membered heteroaryl with O as the heteroatom. 
     
     
       9. A process of claim  2  wherein R 1  is tolyl, anisyl, or naphthyl. 
     
     
       10. A process of claim  2  wherein Y is a unsubstituted or substituted benzene. 
     
     
       11. A process of claim  2 , wherein L is (1S,2S)-N-(2-amino-1,2-diphenyl-ethyl)-4-methyl-benzenesulphonamide. 
     
     
       12. A process of claim  2 , wherein L is (1R,2R)-N-(2-amino-1,2-diphenyl-ethyl)-4-methyl-benzenesulphonamide. 
     
     
       13. A process of claim  2 , wherein L is (1RS,2RS)-N-(2-amino-1,2-diphenyl-ethyl)-4-methyl-benzenesulphonamide (racemic). 
     
     
       14. A process of claim  2 , wherein L is (1S,2S)-N-(2-amino-1,2-diphenyl-ethyl)-4-methoxy-benzenesulphonamide. 
     
     
       15. A process of claim  2 , wherein L is naphthalene-1-sulphonic acid [(1S,2S)-(2-amino-1,2-diphenyl-ethyl)-amide]. 
     
     
       16. A process of claim  2 , wherein L is (1R,2R)-N-(2-amino-cyclohexyl)-4-methyl-benzenesulphonamide. 
     
     
       17. A process of claim 2, wherein L is (1RS,2RS)-N-(2-amino-cyclohexyl)-4-methyl-benzenesulphonamide (racemic). 
     
     
       18. A process of claim  2 , wherein L is N-(2-amino-ethyl)-4-methyl-benzenesulphonamide. 
     
     
       19. A process of claim  2 , wherein L is N-(3-amino-propyl)-4-methyl-benzenesulphonamide. 
     
     
       20. A process of claim  1  wherein an alcohol is used as the hydrogen donor and simultaneously as the solvent. 
     
     
       21. A process of claim  20  wherein the alcohol is a secondary alcohol. 
     
     
       22. A process of claim  21  wherein the alcohol is isopropanol. 
     
     
       23. A process of claim  1  wherein a lower aliphatic halogenated hydrocarbon is used as the solvent in the presence of a hydrogen donor. 
     
     
       24. A process of claim  23  wherein the solvent is methylene chloride or ethylene chloride. 
     
     
       25. A process of claim  23  wherein the solvent is a mixture of formic acid or a salt thereof with triethylamine. 
     
     
       26. A process of claim  2  wherein the ratio of amino-amide-ruthenium complex to (R)-levodione is about 1:20 to 1:10,000 mol:mol. 
     
     
       27. A process of claim  26  wherein the ratio of amino-amide-ruthenium complex to (R)-levodione is about 1:200 to about 1:2000 mol:mol. 
     
     
       28. A process of claim  26  wherein the amino-amide-ruthenium complex is the amino-amide-ruthenium complex of formula I. 
     
     
       29. A process of claim  27  wherein the amino-amide-ruthenium complex is the amino-amide-ruthenium complex of formula I. 
     
     
       30. A process of claim  1  which is effected at a temperature of about 0° C. to about 100° C. 
     
     
       31. A process of claim  30  which is effected at a temperature of about 20° C. to about 50° C. 
     
     
       32. A process of claim  2  wherein the amino-amide-ruthenium complex of formula I is generated in situ during the process from a halogenated precursor.